On Monday, Ms Knox, 24, broke down in sobs as an appeals court in Perugia ruled she and her former boyfriend, Italian computer student Raffaele Sollecito, should be freed immediately.

Ms Knox left Rome shortly before midday (local time) on Tuesday after spending four years in an Italian jail, leaving the family of Ms Kercher to express their anguish at being no closer to the truth about her murder.

The British Airways aircraft carrying Ms Knox and her family landed at Seattle-Tacoma International Airport, where they were expected to address the media after clearing customs.

Small-time Ivorian drug dealer Rudy Guede was convicted of Ms Kercher's murder in 2009 and is serving a 16-year sentence. He lost his appeal but the court is convinced that he did not act alone.

An Italian public prosecutor says he will appeal the acquittal of Ms Knox for the murder of Ms Kercher.

Ms Kercher's family say the search for who killed the British student in 2007 will go on.

"We're still absorbing it. You think you've come to a decision and now it's been overturned," Meredith's mother Arline told reporters at a news conference.

With the acquittals of two people found guilty of murder, Lyle Kercher says there is now confusion about the circumstances of his sister's death.

"We are now obviously left wondering who is the other person or people and it feels for us we're almost back to square one," he said.

Ms Kercher's sister Stephanie said they would wait for the written explanation of the acquittal verdict in the hope that all the killers would eventually be found.

"Once we've got the reasons behind the decisions for this one, then we can understand why they have been acquitted of it and work towards finding those who are responsible," she said.

"That's the biggest disappointment, not knowing still and knowing that there is someone or people out there who have done this."

Investigators believe more than one person was involved in holding Ms Kercher down while she was stabbed and had her throat cut.

'Always grateful'

As she prepared to leave Italy, Ms Knox thanked supporters who believed in her innocence.

"I will always be grateful for their courageous commitment ... [grateful] to those who wrote to me, to those who defended me," she said in a letter to an Italian-American foundation, published by Italian news agency Ansa.

Ms Knox and Mr Sollecito had appealed against a 2009 verdict that found them guilty of murdering 21-year-old Ms Kercher during what prosecutors had said was a drug-fuelled sexual assault four years ago.

British prime minister David Cameron urged people not to forget Ms Kercher's parents.

"Those parents... had an explanation for what had happened to their wonderful daughter, and that explanation isn't there... I think everyone today should be thinking about them and how they feel," he said.

Outside the court on Monday, hundreds of people whistled, booed and shouted "shame, shame" and "bastards" at the courtroom and at US TV crews.

The verdict, an embarrassment for the prosecutor and Italian police investigators, came after independent forensic investigators sharply criticised scientific evidence in the original investigation, saying it was unreliable.

Ms Kercher's half-naked body, with more than 40 wounds and a deep gash in the throat, was found in 2007 in the apartment she shared with Ms Knox in the Umbrian hill town of Perugia where both were studying.

Both Ms Knox and Mr Sollecito, 27, said they were innocent throughout the original investigation and trial.

Mr Sollecito, who had been held in a separate jail near Perugia, also left custody but his lawyer refused to say where he would be spending his first night of freedom.

The court upheld a conviction against Ms Knox for slander, after she had falsely accused barman Patrick Lumumba of the murder.

It sentenced her to three years in prison, a sentence which she has now served.